The proposed studies will focus on the human platelet processes of shape change and primary aggregation. Structural changes which accompany adenosine diphosphate and/or catecholamine hormone-induced shape change will be evaluated using techniques of fluorescence and fluorescence polarization. For these studies, two types of fluorescent probes will be utilized - reactive group specific covalently binding probes, and lipopholic non-covalently binding probes. The processes of primary aggregation in response to alpha-adrenergic hormonal stimulation and inhibition of aggregation by beta-adrenergic hormonal stimulation will be studied. Binding of these hormones to specific surface membrane receptors will be evaluated by: 1. direct binding studies; 2. dose-response aggregation studies, and 3. dose-response studies of adenylyl cyclase stimulation or inhibition. The relationships between adenylyl cyclase activity, cyclic AMP levels, and aggregability will be evaluated. The alpha-adrenergic process of adenylyl cyclase inhibition will be studied and the mechanisms by which this effect is elicited will be sought. The role(s) of calcium in platelet primary aggregation will be studied as will changes in calcium flux which accompany this process. It is hoped that these proposed studies will further elucidate the mechanisms by which extracellular agents regulate cellular functions. In particular, these studies will further clarify blood platelet biochemistry and function and will provide information which may be applied to clinical problems of hemostasis and thrombosis.